Africans drug metabolism

Risperidone and its active metabolite 9-OH-resperidone are metabolized by CYP2D6. Polymorphic metabolism should be considered in those with side effects at low doses (approximately 40% of African Americans and Asians can have increased side effects from risperidone and other drugs metabolized through CYP2D6). 

Orientals are fast acetylators. Separation of individuals into either rapid or slow acetylators is determined by variation at a single autosomal locus and constitutes one of the first discovered genetic polymorphisms of drug metabolism. In general, Eskimos are fast acetylators, while Jews and white North Africans are slow. The half-life of the acetylation reaction for isoniazid in fast acetylators is approximately 70 minutes, whereas in the slow acetylators this value is in excess of 3 hours. 

These differences in clinical response and pharmacokinetics have been attributed to ethnic differences in drug metabolism mediated through the cytochrome P450 microsomal enzyme system, which is responsible for the metabolism of most of the older psychotropic medications, including typical antipsychotics and TCAs (Lin et al. 1993 Silver et al. 1993). Earlier studies showed that Caucasians were more likely than Asians and African Americans to be poor metabolizers of psychotropic medication, a finding inconsistent with clinical experience, because poor metabolizers should require less medication. However, new mutations have recently been discovered in the enzymatic systems of the latter groups that are intermediate in the rate of metabolism. Thus, up to 47%-70% of African Americans and Asian Americans may be slow metabolizers, which could account for the higher incidence of side effects (Mendoza et al. 1999). 

CYP2D6 polymorphism has differential prevalence and effect among population subgroups. For example, CYP2D6 polymorphisms associated with slow drug metabolism are found in approximately 5% to 10% of Caucasians and 1% to 3% of Hispanics, African Americans, and Asian Americans [10]. 

Some indications for plasma level monitoring include inadequate response, relapse, serious or persistent adverse effects, use of higher than standard doses, suspected toxicity, elderly patients, children and adolescents, pregnant patients, patients of African or Asian descent (because of slower metabolism), cardiac disease, suspected noncompliance, suspected pharmacokinetic drug interactions, and changing brands. 

SSRI = Selective serotonin reuptake inhibitor NSAID = Nonsteroidal anti-inflammatory drug CYP = cytochrome P-450 NAT2 = N-acetyl transferase type 2 J = Japanese C = Chinese A = African American. Poor metabolizers are not always at increased risk of ADR. 

Mwenifumbo JC, Sellers EM, Tyndale RF (2007b) Nicotine metabolism and CYP2A6 activity in a population of black African descent Impact of gender and light smoking. Drug Alcohol Depend 89 24-33... 

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